【作者】 李楠；

【导师】 毕锡和；

【作者基本信息】 东北师范大学 ， 有机化学， 2023， 硕士

【摘要】 C-N键广泛存在于药物分子、天然产物和功能材料中。含氮有机化合物,诸如α-氨基酸和生物碱等都具有生物活性,因此C-N键的高效构筑具有重要研究价值。鉴于反应条件温和、官能团耐受性良好和原料易获得,过渡金属催化卡宾的N-H插入反应是目前构筑C-N键的高效方法之一。目前已经发展了铜、铑、铁、钌、铱、钯、金等金属催化的卡宾对胺的N-H插入反应。虽然银催化化学已成为现代有机合成的基石,但目前所发展的银催化N-H键插入反应研究进展有限,主要存在如下问题:底物范围受限（大多局限于缺电子芳胺）,卡宾前体单一,反应机理不明确。我们通过加入配体,促进银卡宾对胺的N-H键插入反应,首次实现了在三溴（三吡唑基）硼(Tp^Br3)配体存在下,银卡宾对脂肪胺的N-H键插入反应;在1,2-环己二胺（DACH）配体存在下,实现银卡宾对富电子芳香的胺N-H键高效插入反应。此外,我们将重氮前体扩展到磺酰腙,可进行克级制备。该方法具有操作简单（空气条件下进行）、反应条件温和、底物范围宽泛、官能团耐受性高等优点。X-射线粉末衍射以及电化学实验印证了DACH通过配位作用降低银中心氧化还原电位,避免银催化剂被还原为单质银,从而稳定银催化剂。另外,通过实验研究和DFT计算表明,胺在反应过程中充当质子穿梭剂,揭示了银催化N-H插入的反应机理。更多还原

【Abstract】 C-N bonds are widely found in natural products,pharmaceutical molecules,and functional materials.Nitrogen-containing organic compounds such asα-Amino acids,alkaloids and nitrogen-containing heterocyclic compounds have a wide range of biological activities,so it is of great significance to develop efficient and convenient methods for the construction of C-N bonds.Given the mild conditions,good tolerance of functional groups,and easy availability of raw materials,transition metal-catalyzed carbene-mediated N-H insertion reaction is one of the most efficient methods to construct C-N bonds at present.To date,N-H insertion reactions of carbene catalyzed by copper,rhodium,iron,ruthenium,iridium,palladium,and gold have been developed.Although silver catalysis has become a cornerstone of modern synthetic organic chemistry,the examples of silver-catalyzed carbene insertion into the N-H bonds are limited to electron-poor aromatic amines and carbene precursors are limited to diazo compounds.The reaction mechanism also needs to be discussed.Herein,we report a ligand-enabled carbene insertion into the N-H bonds of amines under silver catalysis.The achievements include the first silver-catalyzed N-H insertion of aliphatic amines in the presence of tribromo（tripyrazolyl）borate(Tp^Br3)ligand and an efficient N-H insertion of electron-rich aromatic amines using the1,2-diaminocyclohexane（DACH）ligand.We have also extended the diazo precursor to sulfonylhydrazines,which can be prepared in grams.This strategy has the advantages of simple operation under air conditions,mild reaction conditions,wide range of substrates,modular and tolerant to a variety of functional groups.X-ray powder diffraction and electrochemical experiments confirmed that DACH reduces the oxidation-reduction potential of the silver centre through coordination,preventing the silver catalyst from being reduced to simple silver,thus stabilising the silver catalyst.Experimental investigations and DFT calculations showed that DACH stabilises the silver catalyst by reducing its redox potential and the amine may act as a proton shuttle during the reaction,thus revealing an unprecedented mechanism for the silver-catalyzed N-H insertion.更多还原